After cancer battle, researcher Janet Houghton targets new treatments

In a career in cancer research spanning four decades, Southern Research’s Janet Houghton, Ph.D., has studied the mechanics of how drugs attack tumors and investigated the complex inner workings of the disease at a molecular level.

But nothing in her experience could have prepared Houghton – a Distinguished Fellow who was recently named the Emil Hess Endowed Chair in Cancer Biology – for the grim diagnosis her doctor delivered last spring.

The devastating news: Stage IV appendiceal cancer, a malignancy so uncommon that fewer than an estimated 2,500 cases are diagnosed each year. The disease can be deadly. Cancer that originated in the appendix killed actress Audrey Hepburn in 1993 and ESPN sportscaster Stuart Scott in 2015.

“The problem with appendiceal cancer is that you have no symptoms, and it is very advanced by the time it’s diagnosed,” Houghton said. “The hardest part for me was getting my head around what I had. So the acceptance part was a little difficult in the beginning.”

Unlike most patients, though, Houghton’s treatment had deep ties to her own career. As a researcher at St. Jude Children’s Research Hospital in the late 1970s and through the 1980s, she studied the anticancer drug 5-fluorouracil’s mechanism of action and provided insights on how the medicine worked against colon cancer.

Later, Houghton was among the investigators instrumental in advancing the concept that pairing 5-fluorouracil with leucovorin, a derivative of folic acid, would trigger enhanced DNA damage in cancer cells. The combination of the two drugs became the standard treatment for colon cancer in the 1980s.

“I ended up being treated with two of the therapeutic agents I helped develop, which was a little bit of déjà vu, I have to say,” Houghton said. “I took my oncologist several of my own scientific papers and told him that what he was using I spent a good part of my career working on.”

‘MIRACLE RESPONSE’

Houghton’s doctors added two other anticancer drugs — oxaliplatin and Avastin (bevacizumab) — to her treatment protocol. She began her fight.

“Thirty years ago, my diagnosis would have been an absolute death sentence. Without these life-saving drugs, I would not have survived until Christmas. It was quite advanced,” Houghton said.

Her doctors ordered 12 rounds of the combination chemotherapy, a treatment concept that Southern Research’s early cancer research team helped to validate back in the 1960s. The results of Houghton’s treatment were extremely encouraging.

“I had a miracle response. My oncologist was surprised, and so was I. In three months, they estimated I had 90 percent clearance of the disease,” she said.

Houghton prepared herself for a long recovery from an invasive surgical procedure aimed at removing every last trace of cancer from her abdomen, followed by a hot wash of chemotherapy drugs. Once she was in the operating room, there was another surprise. The surgical team couldn’t find any malignant cells to remove.

As a precaution, she went through four additional rounds of chemotherapy. She completed that regimen with minimal side effects. And now with a clean scan and resolution of any remaining abnormalities, today she is on maintenance chemo.

“With the way I have responded to chemotherapy, I’m very optimistic that I could be in that range of patients who are cured,” she added. “The problem is there aren’t many statistics on patients like me because it’s such a rare cancer.”

RENEWED COMMITMENT

Houghton’s encounter with appendiceal cancer has added fuel to her primary research goal — advancing her lab findings along drug discovery lines to produce treatments that save lives.

Southern Research has a strong track record in this area, having discovered seven FDA-approved medicines used in cancer treatment. It was the non-profit’s extensive drug discovery capabilities that lured her to Birmingham in late 2015.

“This life-threatening disease has given my work new meaning. I have always believed that I have and have had a very good life, and I believe in payback, giving something back to people, to our community. It has renewed my commitment to develop new therapeutic agents,” she said.

Supporting her work are earnings from the Emil Hess endowment, established at Southern Research with $1 million in contributions in 1994. Hess, the patriarch of the family that built the Birmingham-based Parisian department store chain, was an early supporter of Southern Research and served on its board.

“Southern Research has earned a well-deserved reputation for groundbreaking discoveries in the battle against cancer, and my father, Emil, would be proud of the accomplishments made through the endowment that carries his name and legacy,” Donald Hess said.

“Janet Houghton is not only a world-class cancer researcher but also a cancer patient herself, so I know she will bring immense talent and energy to this important work,” Hess added.

Houghton said the kind of support she is getting from the Hess endowment is critical to programs like hers. Philanthropic support is instrumental in providing the resources to move research programs forward into the realm of saving lives.

“The research I do has certainly benefited from the Hess endowment and from the funds that I will receive as the endowed chair,” she said. “Because of that support, I can now embark on a drug discovery program.

“It’s amazing what scientists can accomplish with contributions, both large and small.”

THERAPEUTIC TARGETS

A major focus of her research is the role that GLI (pronounced glee) genes have in the origin of cancer cells and how blocking the activation of its proteins in signaling pathways could be exploited as a treatment. Her team sees promise in a prototype molecule, GANT61, which binds exclusively to GLI and has shown the ability to extensively kill cells in human colon cancer cell models.

“That is something I haven’t seen before. I know from our own studies that cancer cells cannot live without GLI,” Houghton said. “I think its protein is actually involved in the transformation process when colonic epithelial cells start forming tumors. I think there are a lot of possibilities if we are successful, including extrapolation to other cancer types.”

In addition, Houghton’s team has identified a second therapeutic target, a protein from the CDT1 gene that’s vital to DNA replication. Southern Research’s high throughput screening system will be utilized to provide a better understanding of its potential for drug discovery.

“I’m optimistic about my future, and I’m optimistic about what I can accomplish here. It’s fitting that I came to Southern Research because of its rich history as a hub for drug discovery. We still have those capabilities now, and we are starting that journey,” she said.

Houghton is determined to turn her experience as a cancer sufferer into a motivational force for her work.

“If there is a hill to climb, I can either do it being miserable, or I can do it with a smile on my face. I decided I was going to be very positive,” she said. “Then my thinking became, how can we take something that could have been potentially bad and turn it into something good?”